2. Academic Validation
  3. Reshaping Intratumoral Mononuclear Phagocytes with Antibody-Opsonized Immunometabolic Nanoparticles

Reshaping Intratumoral Mononuclear Phagocytes with Antibody-Opsonized Immunometabolic Nanoparticles

  • Adv Sci (Weinh). 2023 Oct 22:e2303298. doi: 10.1002/advs.202303298.
Chang Liu 1,  Yanfeng Zhou 1,  Daoxia Guo 1,  Yan Huang 2,  Xiaoyuan Ji 1,  Qian Li 3,  Nan Chen 2,  Chunhai Fan 3,  Haiyun Song 1
Affiliations

Affiliations

  • 1 State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
  • 2 College of Chemistry and Materials Science, The Education Ministry Key Lab of Resource Chemistry, Joint International Research Laboratory of Resource Chemistry of Ministry of Education, Shanghai Key Laboratory of Rare Earth Functional Materials, and Shanghai Frontiers Science Center of Biomimetic Catalysis, Shanghai Normal University, Shanghai, 200234, China.
  • 3 School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China.
PMID: 37867225 DOI: 10.1002/advs.202303298
Abstract

Mononuclear phagocytes (MPs) are vital components of host immune defenses against Cancer. However, tumor-infiltrating MPs often present tolerogenic and pro-tumorigenic phenotypes via metabolic switching triggered by excessive lipid accumulation in solid tumors. Inspired by viral infection-mediated MP modulation, here enveloped immunometabolic nanoparticles (immeNPs) are designed to co-deliver a viral RNA analog and a fatty acid oxidation regulator for synergistic reshaping of intratumoral MPs. These immeNPs are camouflaged with Cancer cell membranes for tumor homing and opsonized with anti-CD163 Antibodies for specific MP recognition and uptake. It is found that internalized immeNPs coordinate lipid metabolic reprogramming with innate immune stimulation, inducing M2-to-M1 macrophage repolarization and tolerogenic-to-immunogenic dendritic cell differentiation for cytotoxic T cell infiltration. The authors further demonstrate that the use of immeNPs confers susceptibility to anti-PD-1 therapy in immune checkpoint blockade-resistant breast and ovarian tumors, and thereby provide a promising strategy to expand the potential of conventional immunotherapy.

Keywords

biomimetic nanoparticle; immunometabolic reshaping; innate immune stimulation; lipid metabolic reprogramming; mononuclear phagocyte.

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